1 -Chlorocarbonyl-4-piperidinopiperidine and hydrochloride thereof are important intermediates as the members of amide group and are used widely in the fields of pharmaceuticals and the like.
As an example of processes for producing 1-chlorocarbonyl-4-piperidinopiperidine or hydrochloride thereof, there is a report by S. Sawada (S. Sawada, Chem. Pharm. Bull., 39, 1446(1991)), whose process is characterized by reacting 4-piperidinopiperidine with a phosgene dimer (TCF), removing an unreacted portion of the phosgene dimer to obtain 1-chlorocarbonyl-4-piperidinopiperidine hydrochloride and, if necessary, treating this hydrochloride with an aqueous solution of a weak base such as sodium bicarbonate or potassium carbonate.
However, this process is not suitable for a large scale production of 1-chlorocarbonyl-4-piperidinopiperidine and hydrochloride thereof, as the phosgene dimer is extremely highly toxic and must be treated using special devices in a special operation area and moreover, its transportation is strictly regulated. In addition, this product is precipitated as a hydrochloride in an agar-like form and the unreacted phosgene dimer takes long time to be filtrated out, leading to a high risk in that operators could be exposed to the toxicity of the phosgene dimer. Furthermore, the yield obtained by this process is poor. Because the precipitated hydrochloride is directly dissolved into the aqueous solution and is hydrolyzed under the condition of a weak base of the aqueous solution, every part of the hydrochlorides cannot be converted to 1-chlorocarbonyl-4-piperidinopiperidine.
An object of the present invention is therefore to provide a highly safe and easily operable process for producing 1-chlorocarbonyl-4-piperidinopiperidine or hydrochloride thereof in a high yield.